Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors

doi:10.1016/j.neuroscience.2009.12.056

Neuroscience

Volume 166, Issue 4, 14 April 2010, Pages 1056-1067

https://doi.org/10.1016/j.neuroscience.2009.12.056 Get rights and content

Abstract

Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior and effort-related choice behavior. Moreover, there is evidence of an interaction between DA D₂ and adenosine A_2A receptor function. Systemic administration of adenosine A_2A antagonists reverses the effects of D₂ antagonists on tasks that assess effort related choice. The present experiments were conducted to determine if nucleus accumbens is a brain locus at which adenosine A_2A and DA D₂ antagonists interact to regulate effort-related choice behavior. A concurrent fixed ratio 5 (FR5)/chow feeding procedure was used; with this procedure, rats can choose between completing an FR5 lever-pressing requirement for a preferred food (i.e., high carbohydrate operant pellets) or approaching and consuming a freely available food (i.e., standard rodent chow). Rats trained with this procedure spend most of their time pressing the lever for the preferred food, and eat very little of the concurrently available chow. Intracranial injections of the selective DA D₂ receptor antagonist eticlopride (1.0, 2.0, 4.0 μg) into nucleus accumbens core, but not a dorsal control site, suppressed FR5 lever-pressing and increased consumption of freely available chow. Either systemic or intra-accumbens injections of the adenosine A_2A receptor antagonist MSX-3 reversed these effects of eticlopride on effort-related choice. Intra-accumbens injections of eticlopride also increased local expression of c-Fos immunoreactivity, and this effect was attenuated by co-administration of MSX-3. Adenosine and DA systems interact to regulate instrumental behavior and effort-related processes, and nucleus accumbens is an important locus for this interaction. These findings may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, anergia and fatigue.

Section snippets

Animals

For all experiments, 132 male Sprague–Dawley rats (Harlan–Sprague–Dawley, Indianapolis, IN, USA) were used. The animals were housed in a colony maintained at 22–24 °C with a 12 h light/12 h dark cycle (lights on at 0700), and housed in pairs before surgery and placed in single cages afterwards. Water was available ad lib in the home cages at all times. The rats that were tested in operant boxes were food restricted to 85% of their free-feeding weight for initial operant training and allowed

Experiments 1 and 2

The results of experiment 1 are shown in Fig. 2A, B. Intra-accumbens injections of eticlopride dose-dependently decreased lever-pressing [F(3, 29)=14.06, P<0.001] and increased consumption of the concurrently available chow [F(3, 29)=10.75, P<0.001]. Planned comparisons revealed that both the 2.0 and 4.0 μg doses of eticlopride significantly decreased lever-pressing and increased chow intake. Furthermore, there was a significant inverse correlation between lever presses and chow intake (r

Discussion

In the present studies, a concurrent lever pressing/chow feeding task was used to characterize the effects of intracranial administration of the D₂ DA receptor antagonist eticlopride, and to examine the interaction between eticlopride and the selective adenosine A_2A receptor antagonist MSX-3. These studies were undertaken to determine whether nucleus accumbens is an important locus for the D₂/A_2A receptor interactions that are involved in effort-related choice behavior. Experiment 1

Conclusion

The present experiments indicate that nucleus accumbens core is an important locus for the involvement of D₂-A_2A receptor interactions in effort-related choice. Nucleus accumbens core injections of eticlopride, but not those given into a dorsal control site, induced the shift from lever pressing to chow intake in rats performing on the concurrent choice procedure. Both systemic and local intra-accumbens core administration of MSX-3 reversed the decrease in lever pressing and increase in chow

Acknowledgments

This research was supported by a grant to JDS from the USA NIH/NIMH (R01MH78023). Merce Correa was supported by a grant of Fundació Caixa Castelló-Bancaixa. Many thanks to Adam Penarolla for his technical assistance.

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¹: Present address: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA.

²: Present address: Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.

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Behavioural NeuroscienceResearch PaperNucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors

Abstract

Section snippets

Animals

Experiments 1 and 2

Discussion

Conclusion

Acknowledgments

Neuroscience

Behav Brain Res

Brain Res Bull

Prog Neuropsychopharmacol Biol Psychiatry

Neuroscience

Behav Brain Res

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Behav Brain Res

Neuroscience

Biol Psychiatry

Neuroscience

Parkinsonism Relat Disord

Trends Neurosci

Parkinsonism Relat Disord

Brain Res Mol Brain Res

Eur J Pharmacol

J Biol Chem

Behav Brain Res

Behav Brain Res

Eur J Pharmacol

Physiol Behav

Brain Res Mol Brain Res

Neuroscience

Pharmacol Biochem Behav

Brain Res

Neuropsychopharmacology

Life Sci

Neuroscience

Trends Cogn Sci

Behav Brain Res

Appetite

Curr Opin Pharmacol

Behav Brain Res

Neurosci Biobehav Rev

Behav Brain Res

Parkinsonism Relat Disord

Brain Res

Neuroscience

Neuroscience

Pharmacol Biochem Behav

Prog Neurobiol

Behav Brain Res

Behav Brain Res

Neural Netw

Brain Res

Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding

Psychopharmacology

Differential regulation of the consummatory, motivational and anticipatory aspects of feeding behavior by dopaminergic and opioidergic drugs

Neuropsychopharmacology

Opioids for hedonic experience and dopamine to get ready for it

Psychopharmacology (Berl)

Dopamine modulates effort-based decision making in rats

Behav Neurosci

Behavioural Neuroscience
Research Paper
Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A_2A and dopamine D₂ receptors